Neurodegenerative disorders (for example, chronic disorders such as Alzheimer's disease, Parkinson'disease, Huntington's disease, Picks's disease, amyotrophic lateral sclerosis and glaucoma as well as acute injuries like stroke, head trauma, Bell's palsy and spinal cord injuries) are now believed to involve apoptotic processes.
Deprenyl, the aliphatic propargylamines, their respective desmethyl analogues and rasagiline have been shown to protect and rescue damaged neurons in several models of degeneration [1-16]. The propargyl group was thought to be a requirement for the protective or rescuing activity of these drugs. Previous studies have examined the N-demethylation and/or depropargylation of these drugs [7, 171].
It has been known for some time that some aliphatic and aromatic acetylenic compounds react with P450 enzymes. One of these reactions results in oxidation of the terminal carbon of the acetylenic functional group to form the corresponding acid [18-20]. The possibility of oxidation of the N-acetylene group of the aliphatic propargylamines to form carboxylic acid metabolites has not been previously addressed. The potential of related acidic compounds (the amino phosphonic acids and amino tetrazoles) and precursors to such compounds (amino nitrites and amino esters) as antiapoptotic agents had also not been previously considered.
The present inventors have found that aliphatic amino carboxylic and amino phosphonic acids, amino nitrites and amino tetrazoles are antiapoptotic agents and may be useful as cellular rescue agents in human and animal treatments.